Reelin' in Clues to Schizophrenia

People with schizophrenia have abnormally low levels of a protein called reelin in the brain. Now researchers have found that this protein seems to play an important role in guiding newborn neurons to their final homes. They suggest that a lack of this protein could lead to schizophrenia by impoverishing neural circuits important for normal cognition--although they and other researchers caution that this mechanism is still speculative.

Researchers knew that reelin plays an important role in brain development because mice that lack the reelin gene have a misshapen cerebral cortex and a peculiar gait (thus the nickname "reeler" mice). They also knew that some psychiatric patients, including schizophrenics, have abnormally low levels of reelin. But scientists have had a hard time figuring out exactly what reelin does.

Preliminary experiments suggested to Kiminobu Sugaya, of the University of Illinois, Chicago, that reelin might help guide new neurons to the correct location in the brain. To test this, he and colleagues injected human neural stem cells into the brains of normal mice and reeler mice. A month later they looked at the brains under a microscope. In the normal mice, the introduced cells had migrated to the hippocampus and cortex, areas critical for cognitive functions such as learning and memory. But in reeler mice, the implanted cells failed to migrate, the team reports in the 19 March issue of the Proceedings of the National Academy of Sciences. Sugaya's team also found evidence that reelin guides the migration of the mice's own stem cells: When they injected mice with a compound that labels newborn cells, they found far fewer new neurons in the hippocampus and cortex of reeler mice. A reelin deficiency--like that seen in schizophrenics--could prevent new-formed neurons from migrating properly and integrating themselves into brain circuits, the team concludes.

The study "adds to the evidence that reelin may be important for neural cell migration," says Lalit Srivastava, a psychiatrist at McGill University in Toronto. But Gabriella D'Arcangelo of Baylor College of Medicine in Houston, who discovered reelin in 1995, says that Sugaya's evidence that the mice's own stem cells migrate to the cortex isn't conclusive and warns that the link between reelin and schizophrenia is still speculative.